A large-scale binding and functional map of human RNA-binding proteins

Van Nostrand Eric L.; Freese Peter; Pratt Gabriel A.; Wang Xiaofeng; Wei Xintao; Xiao Rui; Blue Steven M.; Chen Jia-Yu; Cody Neal A. L.; Dominguez Daniel; Olson Sara; Sundararaman Balaji; Zhan Lijun; Bazile Cassandra; Bouvrette Louis Philip Benoit; Bergalet Julie; Duff Michael O.; Garcia Keri E.; Gelboin-Burkhart Chelsea; Hochman Myles; Lambert Nicole J.; Li Hairi; McGurk Michael P.; Nguyen Thai B.; Palden Tsultrim; Rabano Ines; Sathe Shashank; Stanton Rebecca; Su Amanda; Wang Ruth; Yee Brian A.; Zhou Bing; Louie Ashley L.; Aigner Stefan; Fu Xiang-Dong; Lecuyer Eric; Burge Christopher B.; Graveley Brenton R.; Yeo Gene W.

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A large-scale binding and functional map of human RNA-binding proteins

机译：人RNA结合蛋白的大规模结合和功能图

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A combination of five assays is used to produce a catalogue of RNA elements to which RNA-binding proteins bind in human cells.Many proteins regulate the expression of genes by binding to specific regions encoded in the genome(1). Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.

机译：五种测定的组合用于产生RNA元素的目录，其中RNA结合蛋白在人体细胞中结合。Many蛋白通过结合基因组（1）编码的特异性区域来调节基因的表达。在这里，我们在人类基因组中引入新的RNA元素的新数据集，其被RNA结合蛋白（RBP）识别，所述蛋白质（RBP）产生，作为DNA元素（编码）项目阶段III的细胞内的一部分产生。这类调节元件仅在转录到RNA时起作用，因为它们用作RBP的结合位点，其控制转录后的方法，例如剪接，切割和多腺苷酸化，以及MRNA的编辑，局部化，稳定性和翻译。我们描述了K562和HepG2细胞中大量人Rbps认识到RNA元素的测绘和表征。使用五种测定的整合分析鉴定体内RNA和染色质的RBP结合位点，RBP的体外结合偏好，RBP结合位点的功能和RBP的亚细胞定位，产生1,223个复制的数据集356 RBP。我们描述了在整个转录组中的RBP结合的光谱和这些相互作用与RNA生物学的各个方面的连接，包括RNA稳定性，剪接调节和RNA定位。这些数据通过添加通过与RBP交互在RNA水平上函数的一组元素来扩展人类基因组中编码的功能元素目录。

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《Nature》 |2020年第7818期|711-719|共9页
作者
Van Nostrand Eric L.; Freese Peter; Pratt Gabriel A.; Wang Xiaofeng; Wei Xintao; Xiao Rui; Blue Steven M.; Chen Jia-Yu; Cody Neal A. L.; Dominguez Daniel; Olson Sara; Sundararaman Balaji; Zhan Lijun; Bazile Cassandra; Bouvrette Louis Philip Benoit; Bergalet Julie; Duff Michael O.; Garcia Keri E.; Gelboin-Burkhart Chelsea; Hochman Myles; Lambert Nicole J.; Li Hairi; McGurk Michael P.; Nguyen Thai B.; Palden Tsultrim; Rabano Ines; Sathe Shashank; Stanton Rebecca; Su Amanda; Wang Ruth; Yee Brian A.; Zhou Bing; Louie Ashley L.; Aigner Stefan; Fu Xiang-Dong; Lecuyer Eric; Burge Christopher B.; Graveley Brenton R.; Yeo Gene W.;
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Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

MIT Program Computat & Syst Biol 77 Massachusetts Ave Cambridge MA 02139 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA|Univ Calif San Diego Bioinformat & Syst Biol Grad Program La Jolla CA 92093 USA;

Inst Rech Clin Montreal IRCM Montreal PQ Canada;

UConn Hlth Inst Syst Genom Dept Genet & Genome Sci Farmington CT 06030 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA|Wuhan Univ Med Res Inst Wuhan Peoples R China;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Inst Rech Clin Montreal IRCM Montreal PQ Canada;

Wuhan Univ Med Res Inst Wuhan Peoples R China;

UConn Hlth Inst Syst Genom Dept Genet & Genome Sci Farmington CT 06030 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

UConn Hlth Inst Syst Genom Dept Genet & Genome Sci Farmington CT 06030 USA;

MIT Dept Biol Cambridge MA 02139 USA;

Inst Rech Clin Montreal IRCM Montreal PQ Canada|Univ Montreal Dept Biochem & Mol Med Montreal PQ Canada;

Inst Rech Clin Montreal IRCM Montreal PQ Canada;

UConn Hlth Inst Syst Genom Dept Genet & Genome Sci Farmington CT 06030 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

MIT Dept Biol Cambridge MA 02139 USA;

MIT Dept Biol Cambridge MA 02139 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

MIT Dept Biol Cambridge MA 02139 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

MIT Dept Biol Cambridge MA 02139 USA|MIT Dept Biol Engn 77 Massachusetts Ave Cambridge MA 02139 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

MIT Dept Biol Cambridge MA 02139 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA;

Inst Rech Clin Montreal IRCM Montreal PQ Canada|Univ Montreal Dept Biochem & Mol Med Montreal PQ Canada|McGill Univ Div Expt Med Montreal PQ Canada;

MIT Program Computat & Syst Biol 77 Massachusetts Ave Cambridge MA 02139 USA|MIT Dept Biol Cambridge MA 02139 USA|MIT Dept Biol Engn 77 Massachusetts Ave Cambridge MA 02139 USA;

UConn Hlth Inst Syst Genom Dept Genet & Genome Sci Farmington CT 06030 USA;

Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA|Univ Calif San Diego Inst Genom Med La Jolla CA 92093 USA|Univ Calif San Diego Bioinformat & Syst Biol Grad Program La Jolla CA 92093 USA;

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1. Identification of RNA-binding domains of RNA-binding proteins in cultured cells on a system-wide scale with RBDmap [J] . Castello Alfredo, Frese Christian K., Fischer Bernd, Nature protocols erecipes for researchers . 2017,第12期

机译：用RBDMAP对培养细胞中RNA结合蛋白的RNA结合域的RNA结合结构域
2. Relatedness of an RNA-binding motif in human immunodeficiency virus type 1 TAR RNA-binding protein TRBP to human P1/dsI kinase and Drosophila staufen. [J] . A Gatignol, C Buckler, K T Jeang Molecular and Cellular Biology . 1993,第4期

机译：人免疫缺陷病毒1型TAR RNA结合蛋白TRBP中RNA结合基序与人P1 / dsI激酶和果蝇Staufen的相关性。
3. RBPmap: a web server for mapping binding sites of RNA-binding proteins [J] . Idit Kosti, Inbal Paz, Manuel Ares, Nucleic acids research . 2014,第W1期

机译：RBPmap：用于映射RNA结合蛋白结合位点的Web服务器
4. Scrutinizing functional interaction networks from RNA-binding proteins to their targets in cancer [C] . Sajal Kumar, Hua Zhong, Ruby Sharma, IEEE International Conference on Bioinformatics and Biomedicine . 2018

机译：研究从RNA结合蛋白到其靶标的功能性相互作用网络
5. Characterization of two RNA-binding proteins containing RNA-Recognition Motif (RRM)-type RNA-binding domains from mouse brain. [D] . Inman, Michael Verne. 1999

机译：表征两个RNA结合蛋白的小鼠大脑中的RNA识别基序（RRM）型RNA结合域。
6. RBPmap: a web server for mapping binding sites of RNA-binding proteins [O] . Inbal Paz, Idit Kosti, Manuel Ares Jr, 2014

机译：RBPmap：用于映射RNA结合结合位点的Web服务器蛋白质
7. A large-scale binding and functional map of human RNA-binding proteins [O] . Eric L. Van Nostrand, Peter Freese, Gabriel A. Pratt, 2020

机译：人RNA结合蛋白的大规模结合和功能图

A large-scale binding and functional map of human RNA-binding proteins

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